Poorly differentiated neuroendocrine carcinoma of the seminal vesicle.

We describe an extremely rare case of poorly differentiated neuroendocrine carcinoma arising from the seminal vesicle. A 67-year-old man presented with a left humeral bone tumor resulting in a pathological fracture. Positron emission tomography scan disclosed a large pelvic tumor mimicking prostatic cancer invading into the seminal vesicle. Laboratory data showed an elevation of neuron-specific enolase, despite the normal prostate-specific antigen. Transrectal needle biopsy showed a poorly differentiated carcinoma of the right seminal vesicle and the metastasis of the pelvic lymph node. Immunohistochemical results were compatible with the features of neuroendocrine carcinoma; synaptophysin, chromogranin A and CD 56 were positive. The previously biopsied bone tumor was finally diagnosed as a metastasis. A systemic chemotherapy using etoposide and cisplatin failed. The patient died of cancer one-and-a-half years later.

[Solitary fibrous tumor of the urinary bladder: a case report].

Solitary fibrous tumor (SFT) is one of the mesenchymal tumor usually occurs in the pleura. Extrapleural occurrence of SFT is uncommon. We herein report an extremely rare case of 72-year old man with SFT originated in the urinary bladder. The tumor was incidentally discovered as a mass of 8.5 mm in diameter by a pelvic MRI. Cystoscopy revealed the protruding submucosal tumor in the center of the trigon. Transurethral resection was carried out. Pathological examination revealed a tumor composed of spindle cells with rich vascularity surrounded by abundant collagen fibers. The immunohistochemical findings showed a strong positivity to CD 34 and relatively weak positivity to Bcl-2. MIB-1 index indicated less than 3%, thus the tumor was diagnosed as a solitary fibrous tumor. The patient has no evidence of disease 16 months after the surgery. The current case was the first report in Japan and the twelfth worldwide.

[Validation of 2009 TNM classification based on a prognostic analysis of 350 patients treated for renal cell carcinoma].

PURPOSE: To validate 2009 TNM classification (7th edition) of renal cell carcinoma (RCC), we reevaluated our RCC database depends on 6th and 7th TNM staging and analyzed a prognostic divergence between subgroups. METHODS: A study population of 350 patients with RCC was retrospectively reviewed based on the TNM classification both 6th and 7th editions. Cause-specific survival (CSS) in each group was estimated using Kaplan-Meier method. RESULTS: Applying the new TNM system, 336 patients were divided into pT1a 131, pT1b 105, pT2a 31, pT2b 13, pT3 a 38, pT3b 3, pT3c 0, pT4 14. Previously pT3b-staged 11 cases with renal vein involvement without vena caval extension were included into pT3a. Due to the positive direct invasion into the adrenal gland, previously pT3-staged six patients were changed to pT4. Kaplan-Meier curves revealed no significant differences in CSS between each a/b subgroups from pT1 to pT3. Particularly, no significant statistical value was recognized between pT2a and pT2b subgroups. Patients with direct adrenal invasion tended to show a less favorable prognosis than those with invasion beyond Gerota. CONCLUSIONS: (1) pT2 subdivision does not affect prognostic value. (2) Population imbalance is enhanced due to the pT 3 reclassification. (3) Direct adrenal invasion is compatible with pT4 category.

Curcumin down-regulates AR gene expression and activation in prostate cancer cell lines.

Curcumin, traditionally used as a seasoning spice in Indian cuisine, has been reported to decrease the proliferation potential of prostate cancer cells, by a mechanism that is not fully understood. In the current study, we have evaluated the effects of curcumin in cell growth, activation of signal transduction, and transforming activities of both androgen-dependent and independent cell lines. Prostate cancer cell lines, LNCaP and PC-3, were treated with curcumin and its effects were further analyzed on signal transduction and expression of androgen receptor (AR) and AR-related cofactors using transient transfection assay and Western blotting. Our results show that curcumin down-regulates transactivation and expression of AR, activator protein-1 (AP-1), nuclear factor-kappaB (NF-kappaB), and CREB (cAMP response element-binding protein)-binding protein (CBP). Curcumin also inhibited the transforming activities of both cell lines as evidenced by the reduced colony forming ability in soft agar. The results obtained here demonstrate that curcumin has a potential therapeutic effect on prostate cancer cells through down-regulation of AR and AR-related cofactors (AP-1, NF-kappaB and CBP).

A telomerase-immortalized primary human prostate cancer clonal cell line with neoplastic phenotypes.

Understanding of molecular genetic mechanisms underlying prostate carcinogenesis would be greatly advanced by in vitro models of prostate tumors representing primary tumors. We have successfully established a neoplastic immortalized human prostate epithelial (HPE) clonal culture derived from a primary tumor of a prostate cancer patient (RC-58T) with hTERT, the catalytic subunit of telomerase. The early passage RC-58T cells derived from a radical prostatectomy specimen of a 52-year-old white male patient was transduced through infection with a retrovirus vector expressing the hTERT for the establishment of the RC-58T/hTERT cell line. One clonal line, soft-agar derived from the RC-58T/hTERT cell line, was isolated and further characterized phenotypically and genetically. These clonal (RC-58T/hTERT SA#4) cells are currently growing well at passage 70 and exhibit transformed morphology. The RC-58T/hTERT SA#4 line expressed a high level of telomerase activity and showed anchorage-independent growth in soft agar. The clonal line like the untransduced RC-58T cells (passage 3) expressed prostate specific antigen (PSA), androgen receptor (AR), prostate stem cell antigen (PSCA), and an androgen-regulated prostate specific gene NKX3.1, P16, and cytokeratin (CK) 8. Growth is slightly stimulated by dihydrotestosterone (DHT), and lyates are immunoreactive with AR antibody by Western blot analysis. More importantly, this clonal line produced adenocarcinomas when transplanted into SCID mice. A number of chromosome alterations were observed including the loss of chromosome Y, 1q, 2p, 3p, 4q, 8p, 11p, 14p, 17p and 18q. Our results demonstrate that this primary tumor-derived HPE cell line retained its neoplastic phenotypes and its prostate specific markers and should allow elucidating molecular and genetic alterations involved in prostate cancer. This is the first documented case of an AR and PSA expressing telomerase established human prostate cancer cell line with neoplastic phenotypes from a primary tumor of a prostate cancer patient.

Cadmium-induced neoplastic transformation of human prostate epithelial cells.

Cadmium is a ubiquitous environmental human carcinogen. Epidemiological and animal studies have suggested its carcinogenic potential on the prostate. In the present study, non-tumorigenic human prostate epithelial cells (pRNS-1-1) immortalized by simian papovavirus (SV40) were transformed after repeated exposures to cadmium. Such transformants showed morphological alterations, anchorage-independent growth in soft agar, and formed tumors when transplanted into SCID mice. The tumors were characterized histologically as poorly-differentiated adenocarcinomas, expressing prostate-specific antigen (PSA), androgen receptor (AR), prostate stem cell antigen (PSCA), NKX3.1 and cytokeratin 8 (CK8). These findings provide evidence of malignant transformation of human prostate epithelial cells exposed to this environmentally important chemical.

A novel neoplastic primary tumor-derived human prostate epithelial cell line.

Research into molecular and genetic mechanisms underlying prostate carcinogenesis would be greatly advanced by in vitro models of prostate tumors representing primary tumors. The generation of immortalized primary prostate cancer cells that will accurately reflect the in situ characteristics of malignant epithelium is greatly needed. We have successfully established a neoplastic immortalized human prostate epithelial (HPE) cell culture derived from a primary tumor. The RC-9 cells transduced through infection with a retrovirus vector expressing the E6 and E7 genes (E6E7) of human papilloma virus-16 (HPV-16) are currently growing well at passage 40, whereas RC-9 cells senesced at passage 7. RC-9/E6E7 cells exhibit epithelial morphology and high level of telomerase activity. More importantly, these immortalized cells produced tumors (SCID5038D) when inoculated into SCID mice. RC-9/E6E7 cells and SCID-5038D cells exhibit a high level of telomerase activity and androgen-responsiveness when treated with R1881. Expression of prostate specific antigen (PSA), androgen receptor (AR), prostate stem cell antigen (PSCA), an androgen-regulated prostate specific gene (NKX3.1), p16, cytokeratins 8, 15 and HPV-16 E6 gene was detected in both of these cells. RC-9/E6E7 and SCID5038D cells also showed growth inhibition when exposed to retinoic acid and transforming growth factor (TGF)-beta1, potent inhibitors of prostate epithelial cell growth. A number of chromosome alterations were observed including the loss of chromosomes 2p, 3p, 8p, 13, 14, 16, 17, 18, 21 and the gain of 7 and 20 in the tumor cell line (SCID5038D). These results demonstrate that this primary tumor-derived HPE cell line retained its neoplastic phenotypes and its prostate-specific markers and should allow studies to elucidate molecular and genetic alterations involved in prostate cancer. This is the first documented case of a malignant AR and PSA positive established human prostate cancer cell line from a primary tumor of a prostate cancer patient.

Importance of continuing therapy and maintaining one-month relative dose intensity in sunitinib therapy for metastatic renal cell carcinoma.

Sunitinib is a multikinase inhibitor used as first- and second-line treatment of metastatic renal cell carcinoma. However, there are few reports on the necessary doses of sunitinib to get better clinical outcome in general practice with Japanese patients. We examined the relationship between the efficacy and the necessary doses of sunitinib therapy in a multi-institutional retrospective study. A study population of 94 metastatic renal cell carcinoma patients was eligible for this investigation. The most frequent grade 3/4 laboratory adverse events were decreased platelet (31.9 %) and white blood cell (21.3 %) counts. Treatment was discontinued in 18 patients (31.0 %) initially receiving a 50-mg/day dose within only one course, and median 1-month relative dose intensity was 74.3 %. Median progression-free survival time was 2.3 months in patients treated for only one course and 10.8 months in patients treated for more than one course (P < 0.001). Multivariate analysis showed that only one course of treatment and 60 % and less of 1-month relative dose intensity were significantly associated with inferior progression-free survival (P < 0.001 and P = 0.027, respectively). Moreover, modified Memorial Sloan-Kettering Cancer Center poor risk was significantly associated with progression-free survival time. It is difficult for Japanese patients to continue an initial dose of sunitinib therapy without drug withdrawal. Continuing therapy for more than one course and maintaining more than 60 % of 1-month relative dose intensity were very important in the prolongation of progression-free survival time regardless of the initial treatment doses.

One-month relative dose intensity of not less than 50% predicts favourable progression-free survival in sorafenib therapy for advanced renal cell carcinoma in Japanese patients.

BACKGROUND: Sorafenib is a multikinase inhibitor used as a second-line treatment for metastatic renal cell carcinoma (mRCC). However, it is very difficult to estimate sorafenib dosage because it is difficult to maintain stable administration and dosage intervals due to several side-effects. We examined the correlation between relative dose intensity (RDI) and clinical outcome of sorafenib therapy in a multi-institutional study. METHODS: A study population of 70 first-line therapy-refractory patients with pathologically confirmed RCC was eligible for this investigation. Clinical outcomes were evaluated according to clinicopathological features and RDI for 1 month (1M-RDI). RESULTS: There was significant difference in progression-free survival (PFS) time but not overall survival (OS) time when the 1M-RDI cut-off value was ≥ 50%. In 15 patients (21.4%) with 1M-RDI of <50%, median PFS time was 4.1 months (95% I collagen (95% CI): 2.0-6.2), whereas it was 10.5 months (95% CI: 7.6-13.4) in the patients with 1M-RDI of ⩾50% (P=0.022). Multivariate analysis showed 1M-RDI status to be significantly associated with PFS (HR: 3.838, 95% CI: 1.658-8.883, P=0.002) but not OS (P=0.328). CONCLUSION: Although this study was retrospective, a 1M-RDI cut-off value of ≥ 50% for sorafenib may be the first factor to predict PFS but not OS in cytokine pretreated mRCC patients. The data indicate that a dose of 400mg/day of sorafenib administered successively for the first one month was necessary to prolong disease stabilisation and could be tolerated by Japanese patients.

Needle applicator displacement during high-dose-rate interstitial brachytherapy for prostate cancer.

PURPOSE: To introduce an effective ambulatory technique in high-dose-rate interstitial brachytherapy (HDR-ISBT) for prostate cancer, we investigated the displacement distance using our novel calculation method. METHODS AND MATERIALS: Sixty-four patients treated with HDR-ISBT as monotherapy were examined. Of these, 4, 17, and 43 patients were administered treatment doses of 38 Gy (3 days), 49 Gy (4 days), and 54 Gy (5 days), respectively. For dose administration, we used 776 flexible applicators with a removable template (ambulatory technique). Using CT images, we calculated the relative coordinates of the metal markers and applicators. From these coordinates, to analyze displacement during treatment, we measured the distance between the tip of the needle applicator and the center of gravity of the markers along the average applicator vector. RESULTS: The median displacement distance for all applicators was 7 mm (range, -14 to 24), and that of each treatment schedule was 4, 6, and 9 mm for 38, 49, and 54 Gy, respectively. Of the 776 applicators, displacement of >10 mm was seen in 198 (26%) applicators and >15 mm in 57 (7%) applicators. Body height (p<0.0001) and anticoagulant usage (p<0.0001) were significant factors influencing displacement. CONCLUSIONS: We investigated needle applicator displacement using our unique method. Additional cranial margins are necessary if there is no repositioning of the dwell position. CT scanning should be performed daily during treatment for checking the position of the applicator to detect and rectify the issue of displacement.

Seminal vesicle metastasis of renal cell carcinoma.

We present an unusual magnetic resonance imaging finding of a 70-year-old man with the seminal vesicle tumor. The patient underwent radical nephrectomy for renal cell carcinoma 4 years ago. Laboratory data, including prostatic-specific antigen, ranged within normal limits. Transrectal needle biopsy disclosed a clear cell carcinoma, which was compatible with the original renal cell cancer. Vesiclectomy was performed. Pathohistologic examination confirmed a metastatic renal cell carcinoma of the seminal vesicle.

Antiplatelet therapy and spontaneous perirenal hematoma.

This case report clarifies an adverse reaction of antiplatelet therapy which has been a standard prophylactic method for patients harboring significant risks of thromboembolic events. A 71-year-old Japanese man who had been taking aspirin tablets (81 mg) for a year presented with sudden colic pain in the left flank region. An abdominal computed tomography scan revealed a significant perirenal hematoma of the left kidney. There were no pathological kidney conditions, such as renal tumors, calculi or vascular diseases, found by magnetic resonance imaging examination. After cessation of aspirin administration followed by conservative management, the hematoma completely disappeared 6 months later. This is the first documented case of spontaneous perirenal hematoma secondary to low-dose aspirin treatment. While such unpleasant events occur extraordinarily, this should be noted as a severe risk of antiplatelet therapy.

Adult Wilms' tumor mimicking hemorrhagic renal cyst.

A 36-year-old man presented with macroscopic hematuria associated with right flank pain. Examination of the patient revealed a cystic mass in the right kidney. Because the mass had increased in size, enucleation of the mass was performed. Histopathological findings revealed nephroblastoma, therefore, radical nephrectomy was performed. We believe the pathogenesis of the cystic formation to be a process in which a tumor that had developed in the pericalyceal region spontaneously ruptured, exuding urine into the perinephric space, forming a cystic mass. The patient is alive with no evidence of disease 24 months after the operation.